Abnormal Mineral Metabolism Research Articles

Coexistence of low vitamin D and high fibroblast growth factor-23 plasma levels predicts an adverse outcome in patients with coronary artery disease.

ObjectiveVitamin D and fibroblast growth factor-23 (FGF-23) are related with cardiovascular disorders. We have investigated the relationship of calcidiol (vitamin D metabolite) and FGF-23 plasma levels with the incidence of adverse outcomes in patients with coronary artery disease.MethodsProspective follow-up study of 704 outpatients, attending the departments of Cardiology of four hospitals in Spain, 6–12 months after an acute coronary event. Baseline calcidiol, FGF-23, parathormone, and phosphate plasma levels were assessed. The outcome was the development of acute ischemic events (any acute coronary syndrome, stroke, or transient ischemic attack), heart failure, or death. Cox regression adjusted for the main confounders was performed.ResultsCalcidiol levels showed a moderate-severe decrease in 57.3% of cases. Parathormone, FGF-23, and phosphate levels were increased in 30.0%, 11.5% and 0.9% of patients, respectively. Only 22.4% of patients had glomerular filtration rate<60 ml/min1.73 m2. After a mean follow-up was 2.15±0.99 years, 77 patients developed the outcome. Calcidiol (hazard ratio [HR] = 0.67; 95% confidence interval [CI] = 0.48–0.94; p = 0.021) and FGF-23 (HR = 1.13; 95% CI = 1.04–1.23; p = 0.005) plasma levels predicted independently the outcome. There was a significant interaction between calcidiol and FGF-23 levels (p = 0.025). When the population was divided according to FGF-23 levels, calcidiol still predicted the outcome independently in patients with FGF-23 levels higher than the median (HR = 0.50; 95% CI = 0.31–0.80; p = 0.003) but not in those with FGF-23 levels below this value (HR = 1.03; 95% CI = 0.62–1.71; p = 0.904).ConclusionsAbnormalities in mineral metabolism are frequent in patients with stable coronary artery disease. In this population, low calcidiol plasma levels predict an adverse prognosis in the presence of high FGF-23 levels.

FGF-23 Is a Negative Regulator of Prenatal and Postnatal Erythropoiesis

Abnormal blood cell production is associated with chronic kidney disease (CKD) and cardiovascular disease (CVD). Bone-derived FGF-23 (fibroblast growth factor-23) regulates phosphate homeostasis and bone mineralization. Genetic deletion of Fgf-23 in mice (Fgf-23(-/-)) results in hypervitaminosis D, abnormal mineral metabolism, and reduced lymphatic organ size. Elevated FGF-23 levels are linked to CKD and greater risk of CVD, left ventricular hypertrophy, and mortality in dialysis patients. However, whether FGF-23 is involved in the regulation of erythropoiesis is unknown. Here we report that loss of FGF-23 results in increased hematopoietic stem cell frequency associated with increased erythropoiesis in peripheral blood and bone marrow in young adult mice. In particular, these hematopoietic changes are also detected in fetal livers, suggesting that they are not the result of altered bone marrow niche alone. Most importantly, administration of FGF-23 in wild-type mice results in a rapid decrease in erythropoiesis. Finally, we show that the effect of FGF-23 on erythropoiesis is independent of the high vitamin D levels in these mice. Our studies suggest a novel role for FGF-23 in erythrocyte production and differentiation and suggest that elevated FGF-23 levels contribute to the pathogenesis of anemia in patients with CKD and CVD.

Vascular calcification in long‐term kidney transplantation

Vascular calcification (VC) is common among patients with chronic kidney disease (CKD) due to the strong prevalence of cardiovascular and CKD-related risk factors such as diabetes mellitus (DM), hypertension and phosphate retention. Kidney transplantation improves kidney function and abnormal mineral metabolism at the same time. It remains unclear whether kidney transplantation favourably impacts VC in the long-term. The present study examined VC in 132 kidney transplant (KT) recipients who had been transplanted for longer than one year. The severity of VC was compared to 129 CKD stages 5-5D patients on a kidney transplant (KT) waiting list. The median KT vintage was 88 months. The prevalence of VC among KT and CKD patients were 54.5% and 62.8%, respectively, (P = 0.2). There were no differences in age, gender, body mass index (BMI), the prevalence of DM or CVD between the two groups. Among patients with calcification, a more severe degree was observed in KT recipients (P = 0.01). Aging, DM, CVD and dialysis vintage were associated with significant VC in both groups. The degree of VC in KT recipients was more pronounced than that in CKD patients among those who experienced prolonged dialysis vintage (>2 years) (P = 0.04). Among KT recipients, the severity of VC increased with the length of time after transplantation and became more substantial after 5 years. Long-term KT recipients demonstrated a more severe degree of VC compared to matched CKD stages 5-5D patients. The severity of VC became more pronounced among those with longer transplant vintage and was in part influenced by past dialysis experience.

The Relationship between Intact Parathyroid Hormone Levels and Daily Physical Activity in Hemodialysis Patients

Poor physical activity and decreased daily activities are commonly seen in hemodialysis (HD) patients. Along with the progression of chronic kidney disease (CKD), various abnormalities of mineral and bone metabolism develop, such as osteitis fibrosa and adynamic bone disease, which are related with intact parathyroid hormone (intact-PTH). Surprisingly, scarce data exists regarding the relationship between intact-PTH and daily physical activity in HD patients. Demographics, clinical parameters, laboratory data were recorded for all patients. Depressive symtoms, quality of life and daily activities of HD patients were measured by Beck Depression Inventory, SF-36, and Nottingham Extended Activities of Daily Living Scale (NEADLS), respectively. In total 114 patients (male/female: 63/51, aged: 53.0 ± 13.8 years) were enrolled. The value of intact-PTH for <25th (Group 1), < 25th-50th (Group 2), 50th-75th (Group 3) and >75th (Group 4) quartiles were <132.5 pg/ml, ≥132.5 <261.0, ≥261.0 <510.4 and ≥510.4, respectively. The NEADLS scores were 25.3 ± 10.8, 35.0 ± 9.4, 27.2 ± 13.9 and 26.4 ± 12.9 as going from Group 1 to Group 4 (p = 0.009). Post-hoc analysis of these four groups revealed that only Group 1 and Group 2 (p = 0.012), and Group 2 and Group 4 (p = 0.034) were different with respect to NEADLS scores. Intact-PTH levels were inversely associated with daily activities in whole group. However, the post hoc analysis demonstrated that the association between intact PTH and daily activity is not linear and daily physical activity was lower only in patients with lowest and highest quartiles of intact-PTH.

Cardiovascular co-morbidity in chronic kidney disease: Current knowledge and future research needs.

Chronic kidney disease (CKD) is recognised as a health concern globally and leads to high rates of morbidity, mortality and healthcare expenditure. CKD is itself an independent risk factor for unfavorable health outcomes that include cardiovascular disease (CVD). Coronary artery disease is the primary type of CVD in CKD patients and a significant cause of death among renal transplant patients. Traditional and non-traditional risk factors for CVD exist in patients with CKD. Traditional factors include smoking, hypertension, dyslipidemia and diabetes which are highly prevalent in CKD patients. Non-traditional risk factors of CKD are mainly uraemia-specific and increase in prevalence as kidney function declines. Some examples of uraemia-specific risk factors that have been well documented include low levels of haemoglobin, albuminuria, and abnormal bone and mineral metabolism. Therapeutic interventions targeted at more traditional risk factors which contribute to CVD, have not had the desired effect on lowering CVD events and mortality in those suffering with CKD. Future research is warranted to delineate clear evidence to the benefit of modifying non-traditional risk factors.

Sonographic Evaluation of Secondary Hyperparathyroidism

Secondary hyperparathyroidism (SHPT) is one of the most common abnormalities of mineral metabolism in patients with chronic kidney disease. This case study is a report of a patient referred for sonography based on computed tomography findings of multiple supraclavicular lymph nodes. Sonography was able to localize two enlarged parathyroid glands (adenomas) and to guide fine-needle aspiration for histopathologic tissue diagnosis in this patient with SHPT.

The role of fibroblast growth factor 23 in chronic kidney disease-mineral and bone disorder.

Fibroblast Growth Factor 23 (FGF-23) is a bone-derived hormone involved in the regulation of phosphate homeostasis. FGF-23 levels are extremely elevated in Chronic Kidney Disease (CKD) and there is evidence supporting the role of this hormone in the pathogenesis of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Furthermore, recent data associates FGF-23 with the pathogenesis of systemic complications of CKD-MBD. The increasing evidence that the consequences of abnormal mineral metabolism are not restricted to bone disease changed the approach to the pathophysiology and treatment of disturbed bone and mineral metabolism in CKD patients. FGF-23 has been proposed to be the initial adaptive response in early CKD to protect the organism from the adverse effects of phosphate retention. Increased levels of FGF-23 observed in CKD patients are associated with cardiovascular mortality risk and was shown to mediate direct, "off-target" toxicity to the heart. This report aims to review the relevant aspects of the physiology of FGF-23 in bone biology and mineral homeostasis and the role of FGF-23 in the pathophysiology of CKD-BMD and its clinical implications.

Parathyroidectomy improves cardiovascular outcome in nondiabetic dialysis patients with secondary hyperparathyroidism

Secondary hyperparathyroidism and its associated abnormalities in mineral metabolism and haemodynamic changes increase the cardiovascular risk in patients with end-stage renal disease (ESRD). Our objective was to determine the association of parathyroidectomy (PTX) with major cardiovascular events in nondiabetic dialysis patients with severe secondary hyperparathyroidism (SHPTH). We performed a cohort study with fifty-three nondiabetic ESRD patients who were treated with maintenance haemodialysis and who had intact parathyroid hormone (PTH) levels > 800 pg/ml. Participants received either only medical therapy or medical therapy and total PTX with autotransplantation for SHPTH. We evaluated the associations between PTX and major cardiovascular events including death, cerebrovascular accident and myocardial infarction. The biochemical and haemodynamic changes associated with PTX were measured. During the mean follow-up of 72 months, twenty-three patients received only medical treatment (medical group) while thirty patients underwent PTX in addition to medical treatment (PTX group). The two groups were comparable in respect of baseline characteristics. PTX group was found to be associated with a reduced incidence of major cardiovascular events (P = 0·021). A multiple Cox regression analysis showed that the variable significantly associated with major cardiovascular events was treatment modality (medical therapy vs medical therapy and parathyroidectomy, hazard ratio = 26·12, 95% CI = 1·30-526·27, P = 0·033). Blood pressure, haemoglobin, alkaline phosphatase, calcium, phosphate and calcium × phosphate product significantly improved after PTX. PTX was associated with better cardiovascular outcome in nondiabetic dialysis patients with severe SHPTH.

Abnormal Mineral Metabolism and Mortality in Hemodialysis Patients With Secondary Hyperparathyroidism: Evidence From Marginal Structural Models Used to Adjust for Time-Dependent Confounding

Hemodialysis patients with mineral and bone disorders (MBDs) have an abnormally high relative risk of death, but their absolute risk of death is unknown. Further, previous studies have not accounted for possible time-dependent confounding of the association between MBD markers and death due to the effect of markers of MBD on treatments, which subsequently may affect MBD markers. Multicenter, 3-year, prospective, case-cohort study. 8,229 hemodialysis patients with secondary hyperparathyroidism (parathyroid hormone level ≥180 pg/mL and/or receiving vitamin D receptor activators) at 86 facilities in Japan. Serum phosphorus, calcium, and parathyroid hormone levels. All-cause mortality. Marginal structural models were used to compute absolute differences in all-cause mortality associated with different levels of predictors while accounting for time-dependent confounding. The association between phosphorus level and mortality appeared U-shaped, although only higher phosphorus level categories reached statistical significance: compared to those with phosphorus levels of 5.0-5.9 mg/dL (1.61-1.93 mmol/L), patients with the highest (≥9.0 mg/dL [≥2.90 mmol/L]) phosphorus levels had 9.4 excess deaths/100 person-years (rate ratio, 2.79 [95% CI, 1.26-6.15]), whereas no association was found for the lowest phosphorus category (<3.0 mg/dL [<0.97 mmol/L]; rate ratio, 1.54 [95% CI, 0.87-2.71]). Similarly, hypercalcemia (≥10.0 mg/dL [≥2.50 mmol/L]) was associated with excess deaths, and the highest level of hypercalcemia (≥11.0 mg/dL [≥2.75 mmol/L]) was associated with 5.8 excess deaths/100 person-years (rate ratio, 2.38 [95% CI, 1.77-3.21]) compared to those with levels of 9.0-9.4 mg/dL (2.25-2.37 mmol/L). Abnormally high parathyroid hormone levels were not associated with excess deaths. Possible residual confounding. These results reinforce the idea that serum calcium (in addition to phosphorus) level is an important predictor of the absolute risk of death in hemodialysis patients with secondary hyperparathyroidism.

Racial Differences in Secondary Hyperparathyroidism

Dear Editor, I have recently read an interesting paper by Dr. Seck who had examined the prevalence of CKD-MBD in black African (Senegalese) patients on regular hemodialysis (HD) in a cross-sectional fashion (Nephrol-Urol Mon. 2012; 4(4): 613-616) (1). They showed that 57 out of the 79 patients complicated with CKD-MBD (72%) had a high turnover bone disease with a mean level of 984 pg/mL of intact parathyroid hormone (iPTH). Because mean calcium and phosphorous levels were not elevated (8.6 and 4.85 mg/dL), this marked increment of iPTH may be related to racial differences in the regulation of vitamin D-PTH axis. Autopsy studies have demonstrated that parathyroid mass is increased in blacks compared with whites (2). There is a 4.4-fold higher risk for severe secondary hyperparathyroidism (iPTH > 500 pg/mL) in black patients than in white patients at dialysis initiation (3). African-American HD patients have iPTH levels that are higher than expected in relation to bone histology (4). Blacks with advanced CKD not yet on dialysis also have lower 25(OH)D and higher iPTH concentrations with declining kidney function compared with whites, independent of FGF-23 concentrations (5). So, there may be a unique mechanism by which blacks develop secondary hyperparathyroidism, such as skeletal resistance to PTH, or more activation of calcium-sensing receptor in the parathyroid gland. Although current guidelines on the management of CKD-MBD recommend screening and treating abnormalities in mineral metabolism, none of them take into account for racial differences. Thus, further evaluation will be needed to realize whether current guidelines are truly adequate for all races/ethnicities.

Cinacalcet and Acute Heart Failure on Dialysis - A New Association

Secondary hyperparathyroidism (SHPT) is common in end stage renal disease and is associated with abnormal bone and mineral metabolism, vascular calcification, bone fracture and increased cardiovascular risk. Cinacalcet is an increasingly widely-used calcimimetic agent for the control of SHPT in such patients and trial data has confirmed its use as an efficacious strategy in achieving target parathyroid hormone (PTH) targets. Here we describe a previously undocumented side-effect of cinacalcet treatment in a man on haemodialysis who developed a new and severe dilated cardiomyopathy in clear association with starting cinacalcet. This subsequently resolved fully after withdrawal of the drug. This case, we believe, is the first documented case of severe left ventricular systolic dysfunction temporally associated with cinacalcet use. J Med Cases. 2013;4(6):389-392 doi: https://doi.org/10.4021/jmc1029w

Determinants of Fibroblast Growth Factor-23 and Parathyroid Hormone Variability in Dialysis Patients

Background/Aims: Treatment strategies for abnormal mineral metabolism in chronic kidney disease are largely based on achieving target ranges of biomarkers that vary considerably over time, yet determinants of their variability are poorly defined. Methods: Observational study including 162 patients of three dialysis cohorts (peritoneal dialysis, n = 78; hemodialysis, n = 49; hemodiafiltration, n = 35). Clinical and biochemical determinants of parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) variability were analyzed in the peritoneal dialysis cohort. All cohorts were used for comparison of PTH and FGF23 intra-subject variability (intra-class correlation), and their intra-subject variability in different modes of dialysis was explored. Results: High PTH variability was independently associated with lower 25-hydroxyvitamin D concentration and factors of lipid and glucose metabolism, whereas high FGF23 variability was mainly associated with lower baseline serum phosphorous. These results were consistent in multivariate and sensitivity analyses. The intra-subject variability of FGF23 was lower than for PTH irrespective of dialysis mode. Conclusions: Baseline vitamin D status and serum phosphorous are independent determinants of the longitudinal variation in PTH and FGF23, respectively. The clinical utility of FGF23 measurement remains unknown, yet it appears favorable based on its greater temporal stability than PTH in dialysis patients.

Fibroblast growth factor-23: what we know, what we don't know, and what we need to know

Traditional risk factors of cardiovascular morbidity and mortality such as hypertension, hypercholesterolemia and obesity are paradoxically associated with better outcomes in dialysis patients, and the few trials of interventions targeting modifiable traditional risk factors have yielded disappointing results in this patient population. Non-traditional risk factors such as inflammation, anemia and abnormalities in bone and mineral metabolism have been proposed as potential explanations for the excess mortality seen in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD), but without clear understanding of what the most important pathophysiologic mechanisms of these risk factors are, which ones might be ideal treatment targets and which therapeutic interventions may be effective and safe in targeting them. Among the novel risk factors, fibroblast growth factor-23 (FGF23) has recently emerged as one of the most powerful predictors of adverse outcomes in patients with CKD and ESRD. FGF23 is a hormone produced by osteoblasts/osteocytes in bone that acts on the kidney to regulate phosphate and vitamin D metabolism through activation of FGF receptor/α-Klotho co-receptor complexes. It is possible that elevated FGF23 may exert its negative impact through distinct mechanisms of action independent from its role as a regulator of phosphorus homeostasis. Elevated circulating FGF23 concentrations have been associated with left ventricular hypertrophy (LVH), and it has been suggested that FGF23 exerts a direct effect on the myocardium. While it is possible that 'off target' effects of FGF23 present in very high concentrations could induce LVH, this possibility is controversial, since α-klotho is not expressed in the myocardium. Another possibility is that FGF23's effect on the heart is mediated indirectly, via 'on target' activation of other humoral pathways. We will review the physiology and pathophysiology of FGF23, the outcomes associated with elevated FGF23 levels, and describe putative mechanisms of action responsible for its negative effects and potential therapeutic strategies to treat these.

Small Animal Review

Introduction The management of renal disease requires an understanding of the role that parathyroid hormone plays in abnormal mineral metabolism.

Abstract P137: Walking Impairment and Vitamin D Deficiency in the Elderly, National Health and Nutrition Examination Survey 2001 to 2004

Introduction: Vitamin D deficiency has been reported in 36% of otherwise healthy adults and 57% of inpatients in the US. Vitamin D deficiency (&lt; 15 ng/ml) is linked to increased muscle weakenss, cardiovascular disease and abnormal bone mineral metabolism. The elderly are more prone to vitamin D deficiency because of decrease dietary intake, diminished sunlight exposure and reduced skin thickness among other risk factors. We hypothesized that walking impairment in subjects older than 60 years old is associated to abnormal serum levels of 25-hydroxyvitaminD levels independent of traditional cardiovascular risk factors. Methods: A multivariable adjustment was performed using the National Health and Nutrition Examination Survey database and a graded association was present between serum 25-hydroxyvitaminD levels and walking impairment. We analyzed data from 2,322 participants of the NHANES 2001-2004 survey ages 60 years or older who responded to the walking impairment (WI) questionnaire and had serum 25-hydroxyvitamin D levels measured. Walking impairment was defined as an affirmative answer to the question: “have you had pain in either leg while walking?” A 25 hydroxyvitamin D deficiency level was defined as a serum level of 15ng/dl or less. PAD was defined as an ABI of less than 0.9 in either leg. Results: The prevalence of individuals 60 year or older with walking impairment due to leg pain in the United States is 25 % (S.E, 1.3). Mexican Americans (31.43%) had a higher prevalence of WI than Whites (24.28%) or African Americans (28.67%). Walking impairment was also statistically significant among those with a history of diabetes mellitus, cardiovascular disease, and peripheral arterial disease. Results also showed that C-reactive protein and alkaline phosphates were higher among those with walking impairment. A multivariable adjustment was performed and a graded association was present between serum 25-hydroxyvitaminD levels and walking impairment. An odds ratio of 1.526186(p= 0.013) for walking impairment was present among vitamin D deficient subjects after adjusting for age, gender, and race-ethnicity. The association remained after further adjusting for C-reactive protein, chronic kidney disease, smoking, history of diabetes, PAD, and history of cardiovascular disease (O.R. =1.416255, p=0.045). Conclusion: Walking impairment is associated with 25-hydroxyvitaminD deficiency in the elderly independent of traditional cardiovascular risk factors. These results warrant further studies to determine if vitamin D supplementation improves functional capacity and reduces cardiovascular disease in the elderly.

Hyperparathyroidism in chronic kidney disease patients: an update on current pharmacotherapy

Introduction: Secondary hyperparathyroidism is the most common abnormalities of mineral metabolism in chronic kidney disease (CKD), which causes bone disease and vascular calcification, leading to increased risk of mortality.Areas covered: The aim of this review is to provide an overview of pharmacological therapies for secondary hyperparathyroidism, based on current understanding of the disease.Expert opinion: The initial event in the pathogenesis of secondary hyperparathyroidism is the phosphorus overload per nephron that lead to the secretion of a new phosphaturic hormone, fibroblast growth factor 23 from the bone. Such an abnormality develops very early in CKD, even without hyperphosphatemia. When hyperphosphatemia develops, phosphate binders are prescribed in many CKD patients. Non-calcium containing binders are gaining popularity because of less risk of excess calcium load; however, no specific superiority in patient-level outcomes has been fully established yet. For the direct control of parathyroid hormone secretion, cinacalcet hydrochloride has become widespread in addition to vitamin D receptor activators. As adverse events related to these therapeutic agents occur occasionally, however, and better adherence is one of the most important determinants of the benefits of the drugs, fewer adverse events as well as more potent therapeutic effects should be aimed in the development of new agents in future.

Bone mineral metabolism that kidney controls

With progressive loss of kidney function, patients with chronic kidney disease develop multiple mineral metabolism abnormalities. Chronic kidney disease-mineral and bone disorder independently associated with cardiovascular disease and mortality. FGF23 which discovered in late years gave us new knowledge to elucidate these mechanisms. Further elucidation of FGF23-Klotho will help us to improve the understanding of pathogenesis of bone mineral metabolism abnormality.

Serum FGF23 and Risk of Cardiovascular Events in Relation to Mineral Metabolism and Cardiovascular Pathology

Circulating fibroblast growth factor-23 is associated with adverse cardiovascular outcomes in CKD and non-CKD individuals, but the underlying mechanism remains unclear. This study tested whether this association is independent of mineral metabolism and indices of subclinical cardiovascular pathology. The prospective association between fibroblast growth factor-23 and major cardiovascular events (a composite of hospital-treated myocardial infarction, hospital-treated stroke, or all-cause mortality) was investigated in the community-based Prospective Investigation of the Vasculature in Uppsala Seniors (n=973; mean age=70 years, 50% women) using multivariate logistic regression. Subjects were recruited between January of 2001 and June of 2004. During follow-up (median=5.1 years), 112 participants suffered a major cardiovascular event. In logistic regression models adjusted for age, sex, and estimated GFR, higher fibroblast growth factor-23 was associated with increased risk for major cardiovascular events (odds ratio for tertiles 2 and 3 versus tertile 1=1.92, 95% confidence interval=1.19-3.09, P<0.01). After additional adjustments in the model, adding established cardiovascular risk factors, confounders of mineral metabolism (calcium, phosphate, parathyroid hormone, and 25(OH)-vitamin D), and indices of subclinical pathology (flow-mediated vasodilation, endothelial-dependent and -independent vasodilation, arterial stiffness, and atherosclerosis and left ventricular mass) attenuated this relationship, but it remained significant (odds ratio for tertiles 2 and 3 versus tertile 1=1.69, 95% confidence interval=1.01-2.82, P<0.05). Fibroblast growth factor-23 is an independent predictor of cardiovascular events in the community, even after accounting for mineral metabolism abnormalities and subclinical cardiovascular damage. Circulating fibroblast growth factor-23 may reflect novel and important aspects of cardiovascular risk yet to be unraveled.

Cardiac valve calcification: an immutable pathologic finding in chronic kidney disease?

Although less frequent than vascular calcification, cardiac valve calcification (CVC) is a relevant clinical problem affecting about 2%-10% of adults from the general population aged 75 years and older, and is 5- to 10-fold more prevalent in individuals with impaired kidney function. An expanding body of evidence suggests that mineral metabolism abnormalities aside from traditional cardiovascular risk factors are involved in CVC pathogenesis. Nonetheless, very few studies have investigated whether mineral metabolism manipulation impacts CVC. In this issue of the Journal of Nephrology, it is reported that a combination of low-phosphate diet and sevelamer may reduce CVC. Though the observational nature of that study and the lack of a control group significantly limit the generalizability of these results, they fit in with the ongoing debate on the role of chronic kidney disease mineral bone metabolism (CKD-MBD) in the pathogenesis of vascular disease and suggest the importance of mineral metabolism control in patients with CKD.

Cinacalcet and Acute Heart Failure on Dialysis - A New Association

Secondary hyperparathyroidism (SHPT) is common in end stage renal disease and is associated with abnormal bone and mineral metabolism, vascular calcification, bone fracture and increased cardiovascular risk. Cinacalcet is an increasingly widely-used calcimimetic agent for the control of SHPT in such patients and trial data has confirmed its use as an efficacious strategy in achieving target parathyroid hormone (PTH) targets. Here we describe a previously undocumented side-effect of cinacalcet treatment in a man on haemodialysis who developed a new and severe dilated cardiomyopathy in clear association with starting cinacalcet. This subsequently resolved fully after withdrawal of the drug. This case, we believe, is the first documented case of severe left ventricular systolic dysfunction temporally associated with cinacalcet use. J Med Cases. 2013;4(6):389-392 doi: https://doi.org/10.4021/jmc1029w